Our objective is to investigate the role of the brain in the mechanism of initiation of cardiac arrhythmia, especially ventricular fibrillation, since this arrhythemia is thought to occur in a large group of victims (14 percent of all nontraumatic deaths) for which there exists no pathological evidence to explain their sudden demise. Four central-state variables have been identified and shown by our laboratory to affect cardiac responses and arrhythmias, especially when superimposed upon a background of myocardial ischemia: 1) adaptation to the laboratory, 2) slow-wave and rapid-eye-movement sleep stages, 3) aversive cardiac conditioning, and 4) electrical stimulation of the brain. Our laboratory has developed several new methodologies that will enable us to make unique observations of the effects of certain types of central nervous activity on the myocardium of unanesthetized pigs. Pulsed-Doppler flow transducers and trans-thoracic myocardial freeze- biopsy samples from fully conscious animals will enable us to observe the effects of the central-state variables on coronary flow and tissue metabolism. Intramural and epicardial array electrodes will permit the study of the electrophysiology of the myocardium. Temporary cryogenic blockage of selected brain structures, as well as activation by electrical stimulation, will produce changes in the higher nervous mechanisms whose effects can be monitored in the myocardium. Finally, a method of rapid-freeze biopsy of selected sites will enable changes in brain monoamines to be detected during the imposed central-state conditions. This approach is interdisciplinary, combining behavioral, electrophysiological and biochemical methods.